Impact of the adherence to medical treatment on the main urinary metabolic disorders in patients with kidney stones

Objective:To assess the effect of the adherence to medical treatment on urinary parameters in the 24-h metabolic study of patients with kidney stones.Methods:A retrospective,longitudinal,descriptive,and observational study was carried out by reviewing the hospital electronic medical record from 2014 to 2018.The adherence to drug treatment was measured 6 months after its initiation,and the numerical values of the metabolic studies were compared.Wilcoxon tests were performed to compare the difference before and after treatment.Results:Ninety patients were evaluated,with 73.3% of adherence.The 180-day overall adherence rate was 61.2% in patients treated with a single drug and 85.4% in patients treated with multiple drugs.There is a statistically significant increase in citrate levels in patients with good adherence in comparison with non-adherent patients(p=0.031 vs.p=0.528).Conclusions:Medical treatment and dietary measures in patients with kidney stones have an initial impact at 6 months on the values of the main urinary metabolic alterations that predispose to calculi formation;the most significant is seen in those patients with adherence to medical treatment for hypocitraturia.

Endocrine disrupting chemicals in mixture and obesity,diabetes and related metabolic disorders

Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions. Interestingly, convincing data have shown that environmental pollutants, specifically those endowed with endocrine disrupting activities, could contribute to the etiology of these multifactorial metabolic disorders. Within this review, we will recapitulate characteristics of endocrine disruption. We will demonstrate that metabolic disorders could originate from endocrine disruption with a particular focus on convincing data from the literature. Eventually, we will present how handling an original mouse model of chronic exposition to a mixture of pollutants allowed demonstrating that a mixture of pollutants each at doses beyond their active dose could induce substantial deleterious effects on several metabolic end-points. This proof-of-concept study, as well as other studies on mixtures of pollutants, stresses the needs for revisiting the current threshold model used in risk assessment which does not take into account potential effects of mixtures containing pollutants at environmental doses, e.g., the real life exposure. Certainly, more studies are necessary to better determine the nature of the chemicals to which humans are exposed and at which level, and their health impact. As well, research studies on substitute products are essential to identify harmless molecules.

Liujunzi decoction ameliorats cisplatin-induced anorexia via adjusting metabolic disorders in rats

OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.

Polyhalogenated carbazoles induce hepatic metabolic disorders in mice via alteration in gut microbiota

Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical PHCZs to investigate their negative consequences,along with alternations in gutmicrobiota to indicate underlyingmechanisms.In female mice,the relative liver weight ratio increased after four PHCZs exposure;2-bromocarbazole(2-BCZ)increased urine glucose level;3-bromocarbazole(3-BCZ)decreased the glucose and total cholesterol levels;3,6-dichlorocarbazole(3,6-DCCZ)decreased glucose level.The only disturbed biochemical index in male mice was the promoted alkaline phosphatase(ALP)level by 3,6-DCCZ.We also found that the differential blood biochemical indices were correlated with gut microbiota.3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice,which were correlated with metabolic disorders.Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity andmetabolic disordersmay be due to their dioxin-like potentials and endocrine disrupting activities,and the gender differences might result from their estrogenic activities.Overall,data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.

Epidemiological and Hemato-Biochemical Profiles of Diabetic Patients at the Diabetology, Endocrinology, and Metabolic Diseases Department of the Alpha Oumar Diallo Regional Hospital, Kindia (Republic of Guinea)

This study aims to enhance the healthcare services for diabetic patients in the administrative region of Kindia by suggesting dietary interventions to assist diabetics in better managing their condition. Conducted over a period of six months, from February 18 to July 18, 2021, this prospective and descriptive cross-sectional study involved 220 diabetic patients. Among these, 48 patients (22%) maintained balanced glucose levels (2 g/l). Positive glycosuria was observed in 54% of the patients, whereas 46% demonstrated normal glycosuria. An analysis of urinary parameters revealed that 15% of the patients had abnormal Ketone Bodies. Normal HbA1c levels (9%) HbA1c levels. Hematological assessments indicated significant variation: 56% of the patients had low hemoglobin levels, 4% suffered from hyper-eosinophilia, and 1% each from hyper-basophilia and hyper-hemoglobinemia. The anemic profile was characterized as mild anemia in 75%, moderate anemia in 20%, and severe anemia in 5%. Furthermore, 25% of patients were affected by Microcytic anemia and 75% by Normocytic anemia. Demographically, women constituted 65% of the study group compared to 35% of men. The most represented age bracket was 41 to 60 years, accounting for 52% of the patients, while those between 61 and 80 years comprised 36%. Every district in Kindia was impacted by diabetes.

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

Comparison of Drospirenone-with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders： A Prospective Randomized Control Trial

Background：While combined oral contraceptives （COCs） are commonly used to treat polycystic ovary syndrome （PCOS）,comparative data regarding metabolic effects of different progestogens on this patient population are missing.This study aimed to compare the different effects of drospirenone （DRP）-containing COCs with cyproterone acetate （CPA）-containing COCs,combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders.Methods：Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial.Participants were randomized into two groups such as DRP-containing COCs,and CPA-containing COCs.Participants took COCs cyclically for 6 months,combined with metformin administration （1.5 g/d） and lifestyle modifications （diet and exercise）.Clinical measures and biochemical and hormone profiles were compared.Comparisons for continuous variables were evaluated with paired and unpaired Student＆#39;s t-tests.The Wilcoxon signed rank test was used when the data were not normally distributed.Analysis of covariance was used to control for age,body mass index （BMI）,and baseline data of each analyzed parameter when compared between the two groups.Results：A total of 68 patients have completed the study.The combination regimen of COCs,metformin,and lifestyle modifications in these patients resulted in a significant decrease in BMI,acne,and hirsutism scores when compared to baseline levels in both groups （P 〈 0.05）.Blood pressure （BP） was significantly different in the CPA group when compared to baseline （75.14 ± 6.77 mmHg vs.80.70 ± 5.60 mmHg,P 〈 0.01）,and after 6 months of treatment,only the change in systolic BP was significantly different between the two groups （4.00 [-6.00,13.00] mmHg vs.-3.50 [-13.00,9.00] mmHg,P =0.009）.Fasting glucose,fasting insulin,and homeostasis model assessment-insulin resistance decreased significantly in the DRP group （5.40 ± 0.41 mmol/L vs.5.21 ± 0.32 mmol/L,P =0.041;13.90 [10.50,18.40] μU/ml vs.10.75 [8.60,13.50] μU/ml,P =0.020;3.74 [2.85,4.23] vs.2.55 [1.92,3.40],P =0.008） but did not differ between the two groups.While individual lipid profiles increased in both groups,no statistically significant difference was observed.Conclusions：DRP-containing COCs combined with metformin and lifestyle modifications could better control BP and correct carbohydrate metabolism in women with PCOS and metabolic disorders compared with CPA-containing COCs.

Prevalence of stroke and metabolic disorders in the middle-aged and elderly Chinese with type 2 diabetes

Background Stroke is now the most prevalent and debilitating disease affecting diabetic population in China. The study aimed to investigate the prevalence of stroke and metabolic disorders in the middle-aged and elderly Chinese with type 2 diabetes. Methods A total of 4 629 subjects with type 2 diabetes （males： 1 917; females： 2 712） aged ≥ 40 years from Shijingshan district, Beijing, China from November 2011 to August 2012 were included in the study. Data on demographic information, lifestyle, history of diabetes mellitus, stroke, coronary heart disease, hypertension, and dyslipidemia were collected. The oral glucose tolerance test or a standard meal test was performed. Non-fatal stroke was reported by the subjects. The 2-tailed test was used, and P 〈0.05 was regarded as statistically significant. Results Prevalence of stroke in the subjects with type 2 diabetes was 5.5%. The prevalence of smoking, overweight or obesity, hypertension, and dyslipidemia was 41.0%, 65.8%, 67.4%, and 52.0% in males, and 2.2%, 65.5%, 69.5%, and 57.6% in females. Multivariate Logistic regression analysis showed that increased age, hypertension, diabetic duration, and overweight or obesity were positively correlated with stroke in the population with type 2 diabetes, whereas high- density lipoprotein cholesterol level was negatively correlated with stroke. After adjustment for age and gender, the odds ratio values of stroke in subjects having 1,2 or ≥3 of 4 risk factors, including smoking, overweight or obesity, hypertension and dyslipidemia, were 2.302 （95% CI： 0.789-6.712）, 4.089 （95% CI： 1.470-11.373）, 6.023 （95% CI： 2.176-16.666）, compared with subjects without any of the above 4 risk factors. Conclusions The prevalence of stroke was higher in middle-aged and eldedy Chinese with type 2 diabetes than that in the general population. With the aggregation of risk factors, the prevalence of stroke increased.

Metabolic disorders of fatty acids and fatty acid amides associated with human gastric cancer morbidity

Background Gastric cancer （GC） is one of the most common types of cancer in the world. A change in the metabolism of lipids in tumor cells could lead to the pathogenesis of cancer. In this study, we investigated fatty acid and fatty acid amide metabolic perturbations associated with GC morbidity.

Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome

With the support by the National Natural Science Foundation of China,the research team led by Prof.Wang Di(王迪)at the Immuno metabolism Lab,Institute of Immunology,Zhejiang University School of Medicine,uncovered the mystery of Bile Acids control inflammation and metabolic disorder,which was published in Immunity(2016,45:802—816)).

The journey of gut microbiome - An introduction and its influence on metabolic disorders

BACKGROUND： Metabolic disorders such as Obesity, Diabetes Type 2 （T2DM） and Inflammatory Bowel Diseases （IBD） are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague. OBJECTIVE： The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota. METHODS： A methodical PubMed search was performed using keywords like ＂gut microbiome,＂ ＂obesity, diabetes,＂ ＂IBD,＂ and ＂metabolic syndromes.＂ All significant and latest publications up to January 2018 were accounted for the review. RESULTS： Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant （FMT）. CONCLUSION： Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.

Prediction of Metabolic Disorders Using NMR-Based Metabolomics:The Shanghai Changfeng Study

A metabolically healthy status,whether obese or not,is a transient stage with the potential to develop into metabolic disor-ders during the course of life.We investigated the incidence of metabolic disorders in 1078 metabolically healthy Chinese adults from the Shanghai Changfeng Study and looked for metabolites that discriminated the participants who would develop metabolic disorders in the future.Participants were divided into metabolically healthy overweight/obesity(MHO)and meta-bolically healthy normal weight(MHNW)groups according to their body mass index(BMI)and metabolic status.Their serum metabolomic profile was measured using a ^(1)H nuclear magnetic resonance spectrometer(^(1)H-NMR).The prevalence of diabetes,hypertriglyceridemia,hypercholesterolemia and metabolic syndrome was similar between the MHNW and MHO participants at baseline.After a median of 4.2 years of follow-up,more MHO participants became metabolically unhealthy than MHNW participants.However,a subgroup of MHO participants who remained metabolically healthy(MHO→MHO)had a similar prevalence of metabolic disorders as the MHNW participants at the follow-up examination,despite a signifi-cant reduction in their serum concentrations of high-density lipoprotein(HDL)and an elevation in valine,leucine,alanine and tyrosine.Further correlation analysis indicated that serum intermediate-density lipoprotein(IDL)and very low-density lipoprotein cholesterol(VLDL-CH)might be involved in the transition from metabolically healthy to unhealthy status and could be valuable to identify the MHNW and MHO with increased metabolic risks.

Impact of body mass index,weight gain,and metabolic disorders on survival and prognosis in patients with breast cancer who underwent chemotherapy

Background: Weight gain during chemotherapy in patients with breast cancer contributes to their poor prognosis. However, a growing number of studies have found that metabolic disorders seem to play a more important role in breast cancer prognosis than weight gain. This study aimed to explore the prognostic effects of body mass index (BMI), weight gain, and metabolic disorders on the overall survival (OS) and prognosis of patients with breast cancer who underwent chemotherapy.Methods: Data from the inpatient medical records of patients with breast cancer who underwent chemotherapy at the Beijing Cancer Hospital Breast Cancer Center from January to December 2010 were retrospectively collected, and the patients were followed up until August 2020.Results: A total of 438 patients with stages I to III breast cancer met the inclusion and exclusion criteria. Forty-nine (11.19%) patients died, while 82 (18.72%) patients had tumor recurrence and metastasis at the last follow-up (August 2020). From the time of diagnosis until after chemotherapy, no significant differences were observed in the body weight (t=4.694,P<0.001), BMI categories (χ^(2)=19.215,P=0.001), and incidence of metabolic disorders (χ^(2)=24.841,P<0.001);the BMI categories and weight change had no effect on the OS. Both univariate (χ^(2)=6.771,P=0.009) and multivariate survival analyses (hazard ratio=2.775, 95% confidence interval [CI]: 1.326-5.807,P=0.007) showed that low high-density lipoprotein cholesterol (HDL-C) levels at diagnosis had a negative impact on the OS. The multivariate logistic regression analysis showed that the HDL-C level at diagnosis (odds ratio [OR]=2.200, 95% CI: 0.996-4.859,P=0.051) and metabolic disorders after chemotherapy (OR=1.514, 95% CI: 1.047-2.189,P=0.028) are risk factors for poor prognosis in patients with breast cancer.Conclusions: Chemotherapy led to weight gain and aggravated the metabolic disorders in patients with breast cancer. Low HDL-C levels at diagnosis and metabolic disorders after chemotherapy may have negative effects on the OS and prognosis of patients with breast cancer.

Advanced glycation end product signaling and metabolic complications:Dietary approach

Advanced glycation end products(AGEs)are a heterogeneous collection of compounds formed during industrial processing and home cooking through a sequence of nonenzymatic glycation reactions.The modern western diet is full of heat-treated foods that contribute to AGE intake.Foods high in AGEs in the contemporary diet include processed cereal products.Due to industrialization and marketing strategies,restaurant meals are modified rather than being traditionally or conventionally cooked.Fried,grilled,baked,and boiled foods have the greatest AGE levels.Higher AGE-content foods include dry nuts,roasted walnuts,sunflower seeds,fried chicken,bacon,and beef.Animal proteins and processed plant foods contain furosine,acrylamide,heterocyclic amines,and 5-hydroxymethylfurfural.Furosine(2-furoil-methyl-lysine)is an amino acid found in cooked meat products and other processed foods.High concentrations of carboxymethyl-lysine,carboxyethyl-lysine,and methylglyoxal-O are found in heat-treated nonvegetarian foods,peanut butter,and cereal items.Increased plasma levels of AGEs,which are harmful chemicals that lead to age-related diseases and physiological aging,diabetes,and autoimmune/inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis.AGEs in the pathophysiology of metabolic diseases have been linked to individuals with diabetes mellitus who have peripheral nerves with high amounts of AGEs and diabetes has been linked to increased myelin glycation.Insulin resistance and hyperglycemia can impact numerous human tissues and organs,leading to long-term difficulties in a number of systems and organs,including the cardiovascular system.Plasma AGE levels are linked to all-cause mortality in individuals with diabetes who have fatal or nonfatal coronary artery disease,such as ventricular dysfunction.High levels of tissue AGEs are independently associated with cardiac systolic dysfunction in diabetic patients with heart failure compared with diabetic patients without heart failure.It is widely recognized that AGEs and oxidative stress play a key role in the cardiovascular complications of diabetes because they both influence and are impacted by oxidative stress.All chronic illnesses involve protein,lipid,or nucleic acid modifications including crosslinked and nondegradable aggregates known as AGEs.Endogenous AGE formation or dietary AGE uptake can result in additional protein modifications and stimulation of several inflammatory signaling pathways.Many of these systems,however,require additional explanation because they are not entirely obvious.This review summarizes the current evidence regarding dietary sources of AGEs and metabolism-related complications associated with AGEs.

A novel function of CREG in metabolic disorders

Metabolic disorders are public health problems that require prevention and new efficient drugs for treatment.Cellular repressor of E1A-stimulated genes(CREG)is ubiquitously expressed in mature tissues and cells in mammals and plays a critical role in keeping cells or tissues in a mature,homeostatic state.Recently,CREG turns to be an important mediator in the development of metabolic disorders.Here in this review,we briefly discuss the structure and molecular regulation of CREG along with the therapeutic strategy to combat the metabolic disorders.

Metabolic Emergencies in Newborns in a Subsaharian Neonatology Department: Evaluation of Glucose, Sodium and Potassium Disorders

Introduction: Metabolic neonatal adaptation is a complex phenomenon and metabolic disorders can be frequent in immature newborns or in life-threatening situations. In Low and Middle income countries (LMIC) the difficult access to some diagnostic tests makes the management of the metabolic emergencies challenging. The main objectives of this study were to assess the frequency and circumstances of occurrence and to describe the clinical picture associated with glucose, sodium and potassium disorders in neonates. Patients and Methods: Our study was a retrospective and descriptive study conducted in the neonatology unit of National Children Hospital Albert Royer in Dakar (Senegal) from January 1 to December 31, 2014. Results: The prevalence of the studied metabolic disorders was 46.7%. The most common metabolic disorder noted was Hyperglycemia followed by Hyponatremia. Thermoregulation disturbances were found particularly in newborns with serum sodium disorders (hyponatremia 33.5% and hypernatremia 59.7%). Neurological signs were noted in case of blood sugar abnormalities (hypoglycemia 26.1% and hyperglycemia 29.8%). Half of the newborns with hyperglycemia (82 cases/50%) had blood sugar levels greater than or equal to 2 g/l. Hypernatremia was severe (Serum sodium> 180 mmol/l) in 12 neonates (16.7%). The main diagnoses retained were sepsis (159 cases/45.4%), prematurity (96 cases/27.4%), intrauterine growth retardation (66 cases/18.9%), malformations (63 cases/18%), perinatal asphyxia (44 cases/12.6%) and malnutrition (36 cases/10.3%). For most metabolic disorders, the correction was late and was done beyond 48 hours. On average, the correction time varied between 3 hours and 6 days. The most frequent complications were cerebral edema (12 cases), brain death (8 cases) and increased intracranial pressure (3 cases). The most lethal disorders were Hyperkalemia followed by Hyperglycemia. Conclusion: Metabolic disorders especially glucose, sodium and potassium disorders are common in newborns. They are medical emergencies that can lead to vital instability and death. Their management is challenging in low-income countries due to the lack of adapted facilities and means to diagnose them. It is therefore important to improve the availability of technical methods and means of biological analysis in hospital laboratories and to monitor closely all newborns for early diagnosis of these disorders.

Huangqin decoction alleviates lipid metabolism disorders and insulin resistance in nonalcoholic fatty liver disease by triggering Sirt1/NF-κB pathway

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.

Implications of metabolic dysfunction associated fatty liver disease in COVID-19

Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.

Roles of fibroblast growth factors in the treatment of diabetes

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

Liver transplantation for pediatric inherited metabolic liver diseases

Liver transplantation(LT)remains the gold standard treatment for end stage liver disease in the pediatric population.For liver based metabolic disorders(LBMDs),the decision for LT is predicated on a different set of paradigms.With improved outcomes post-transplantation,LT is no longer merely life saving,but has the potential to also significantly improve quality of life.This review summarizes the clinical presentation,medical treatment and indications for LT for some of the common LBMDs.We also provide a practical update on the dilemmas and controversies surrounding the indications for transplantation,surgical considerations and prognosis and long terms outcomes for pediatric LT in LBMDs.Important progress has been made in understanding these diseases in recent years and with that we outline some of the new therapies that have emerged.